How Early Manufacturing Decisions Shape Long-Term Success

By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1

Bringing cell therapies from concept to clinic is a complex, high-stakes endeavor, as every early manufacturing decision can echo through the entire product lifecycle. The challenge lies in moving fast enough to reach first-in-human trials while building processes that can withstand regulatory scrutiny and scale for commercialization.

I had the pleasure of discussing this important topic with Todd Luman, Executive Director of Process and Product Development at Allogene Therapeutics, and Raymond Luke, Senior Director of MSAT at Verismo Therapeutics during our most recent Cell & Gene Live, Designing Early Manufacturing For Long-Term Success In CGT. While Verismo focuses on autologous therapies, Allogene specializes in allogeneic platforms, so our conversation was a unique opportunity to compare approaches across both modalities.

Setting the Foundation Early

Luman began emphasizing that teams should view development in a single-cycle paradigm. He explained, “It’s very difficult in the cell and gene therapy space to make pivotal process changes later on due to comparability considerations.” He shared that the organizations that invest in the right areas early on could save time, cost, and significant operational friction further down the line.

Luke concurred but cautioned against overengineering in early phases. “There isn’t a crystal ball that will tell you exactly what you need in the future for your product or your process,” he said. “You have to be as Nostradamus as possible.” His advice: start simple, collect as much data as possible, and maintain flexibility. “Building in complexity too soon can reduce automation potential and scalability later,” he noted.

Balancing Flexibility with GMP and Tech Transfer

When discussing how to align early development with GMP standards and tech transfer, Luke pointed to the importance of understanding “phase-appropriate differences.” He stressed that risk-based thinking shapes every decision: “That doesn’t mean stop; it means understand the risks so you can lay out a roadmap for commercialization.”

Luke also underscored the importance of process simplicity. “A lot of these processes are developed by PhDs in labs, but they end up in clean rooms staffed by early-career technicians. Making sure your process is robust enough is key, and simplicity really is key.”

Luman, representing the allogeneic view, agreed that communication and documentation are crucial. “As we develop the process, we build out our process description as we go,” he explained. His team works closely with manufacturing early on to translate those process descriptions into master batch records. “Don’t assume anything. The details matter, and how those translate onto the manufacturing floor can be consequential.”

How Early Decisions Shape Downstream Success

Both speakers emphasized the profound downstream effects of early-stage choices. Luman said that product quality and safety decisions should always come first. “If you choose to do cell isolations, do that early,” Luman stated. “Your cytokine mix or media background will heavily influence how your cells evolve.” In parallel, he urged ensuring robust and defendable gene-editing methods from the start of development.

Luke expanded from his autologous experience, cautioning that early reliance on all-in-one platforms can limit adaptability. “Oftentimes that traps you in an inflexible system, and making changes later becomes far more difficult,” Luke said. He added that the lack of comprehensive data collection early on could mean you’re missing something critical, making flexibility a long-term asset rather than a liability.

Futureproofing the Manufacturing Process

When I questioned our expert panelists about how developers should future-proof their processes, Luke emphasized understanding risk and pain points. “With a strong grasp of where your process struggles, from compliance to scaling, you can design a roadmap for continuous improvement,” he said.

Luman agreed but noted that the allogeneic model presented unique consistency challenges. “We make many lots from unique donors, but those lots need to be representative of each other,” Luman said. He described controlling for “donor variation, supply chain robustness, and genetic modification reproducibility” as essential pillars. “Every lot has to meet the same quality expectations as the last,” he added.

The Role of Data as the Backbone of Decision-Making

Luke called data the backbone of modern therapy development, stressing that small or lean companies couldn’t afford to delay investment in analytics. “If you fail to collect enough data early, you won’t be able to make evidence-based changes later,” Luke warned. He advised capturing all of the data, even what seems meaningless, because hidden correlations might later prove vital for regulatory or clinical insight.

He also encouraged cross-functional collaboration. “You want to understand your product from end to end - what comes in, how it performs through manufacturing, and how it translates in the patient,” Luke said.

Luman extended that theme to smaller firms. “You don’t get as many chances on goal,” he said. He recommended early investments in structured data management systems, adding, “Get everyone on board,” he said. “If you call one attribute something different across datasets, your analytics will fall apart.” Indeed, his advice for startups was pragmatic. “Focus on the science, not coding. Use proven visualization tools so you can spend your time developing therapies rather than troubleshooting spreadsheets.”

Automation, Flexibility, and Process Scale-Up

Automation and scalability formed another major thread in the discussion. Luman emphasized the need for equipment flexibility, noting that allogeneic therapies must balance between yield, scalability, and commercial practicality. “There isn’t a one-size-fits-all solution. Maintaining flexibility lets you adapt as the science and tools evolve.”

Luke fully agreed, describing rigid automated solutions as double-edged swords. “You don’t want to fit your product into the process. You want your process to fit the product,” he said. “Semi-automated systems can help maintain that flexibility, and new robotics and adaptive software will allow easier scale-out in the future.” He warned that by the time companies reached commercialization, many “all-in-one” systems could already be outdated.

Innovation and Technological Readiness

As conversation turned to innovation, both speakers emphasized the value of foresight. “Ideally,” Luman explained, “you design your facilities and processes so they’re amenable to adopting emerging technologies like advanced analytics or digital twins.” Luke added that even if a company wasn’t ready to use advanced analytics immediately, it should at least collect and bank samples systematically. “If those samples aren’t there, you’ll never have another chance to go back and do advanced characterization later,” said Luke.

Luman echoed the importance of thoughtful retention strategies. “It’s a burden to store cell therapy samples, but when new technologies come along, those retained samples become invaluable.”

A Shared Vision for the Future

Both experts shared cautious optimism about the evolving landscape. “We believe in allogeneic,” Luman said. “It has the potential to make truly efficacious therapeutics available for every patient in need.” He predicted that future innovations might not just improve gene modification but even influence phenotype to overcome tumor microenvironment barriers.

Luke envisions a future driven by smarter, safer, and more robust design. “It’s about better safety, better efficacy, and lower cost,” he said. “And that starts from day one, in how we think about development.”

Together, Luman and Luke captured a truth shaping the forefront of biotechnology: that the success of tomorrow’s therapies depends not just on discoveries but on discipline. They agree that early choices, grounded in science and data, ripple through every phase of bringing transformative therapies to patients.

Be sure to check out the full-length Cell & Gene Live to learn more from the detailed discussion.